Background: Stress is highly prevalent among young adults aged 18–25 years due to academic, social, and emotional challenges. Recent research suggests that genetic factors, including ABO and Rh blood groups, may influence individual susceptibility to stress. Aim: To evaluate the association between ABO and Rh blood groups and stress levels among individuals aged 18–25 years. Materials and Methods: A cross-sectional, questionnaire-based study was conducted at KMCRI College, Hubli, over a period of 6 months. A total of 150 participants were included using convenience sampling. Data regarding demographic profile and blood group were collected, and stress levels were assessed using the Perceived Stress Scale (PSS-10). Statistical analysis was performed using SPSS, and associations were tested using the Chi-square test. Results: The majority of participants were aged 20–21 years (30.7%), with a slight male predominance (54.7%). Blood group O (37.3%) was the most common, and most participants were Rh positive (88.0%). Moderate stress was observed in 52.0% of participants. A statistically significant association was found between ABO blood group and stress levels (p = 0.021), while gender and Rh factor showed no significant association. Conclusion: ABO blood group may play a role in stress susceptibility among young adults. Further studies are required to establish causal relationships.